Chronic Obstructive Pulmonary Disease (COPD) as a Risk Factor for Glucose Metabolism Perturbation and Insulin Resistance

Background: High body mass index (BMI) is associated with better survival in COPD. However, increased BMI and especially waist circumference is associated with elevated pro-inflammatory systemic markers that might contribute to glucose intolerance. On the other hand, COPD is a chronic inflammatory disease that could be a risk factor for impaired glucose metabolism. The objective of this study was to compare the prevalence of glucose intolerance in COPD patients and control subjects with high waist circumference. Methods: Eleven patients with COPD (age:68±8 yr mean±SD; FEV1:49±17% pred) and 10 control subjects (C) (age:63±6 yr) underwent a 75g oral glucose tolerance test (OGTT). All subjects had a waist circumference >102cm and no previous history of diabetes. Height and weight were measured and each subject underwent dual-energy X-ray absorptiometry (DEXA) to evaluate fat-free mass (FFM) and fat mass (FM) and abdominal tomography to evaluate visceral fat (VF). Blood samples were taken to measure inflammatory markers (C-reactive protein (CRP), tumor necrosis factor (TNF), interleukin (IL)-6). Venous blood samples of glucose and insulin were taken while fasting and during OGTT. Insulin resistance was estimated with the fasting homeostasis model assessment (HOMA) index. Results: FM, FFM and VF were not different between groups. Diabetes was diagnosed in two subjects in both groups (2hr post OGTT glucose ≥11.1 mmol/l). Four COPD and 1 C had impaired fasting glucose (fasting glucose 5.6–6.9 mmol/l) while 1 COPD and 2 C had impaired glucose tolerance (2hr post OGTT glucose 7.8–11.1 mmol/l). In COPD patients a negative correlation was found between the HOMA index and FEV1 (r2:0.52, P < 0.05). Conclusions: COPD subjects with high waist circumference are similar to control subjects in term of FFM and FM, level of systemic inflammation and response to OGTT. In COPD, the severity of the disease is associated with an insulin resistance that may potentiate the risk for the development of type 2 diabetes in these patients.

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Physical Activity, Measures of Obesity, and Cardiometabolic Risk: The Multi-Ethnic Study of Atherosclerosis (MESA)

Journal of Physical Activity and Health ◽

10.1123/jpah.2012-0068a ◽

2014 ◽

Vol 11 (4) ◽

pp. 831-837 ◽

Cited By ~ 9

Author(s):

Paul A. McAuley ◽

Haiying Chen ◽

Duck-chul Lee ◽

Enrique Garcia Artero ◽

David A. Bluemke ◽

...

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Waist Circumference ◽

Impaired Fasting Glucose ◽

Central Obesity ◽

Cardiometabolic Risk ◽

Fasting Glucose ◽

Reference Group ◽

Model Assessment ◽

Ethnic Study

Background:The influence of higher physical activity on the relationship between adiposity and cardiometabolic risk is not completely understood.Methods:Between 2000–2002, data were collected on 6795 Multi-Ethnic Study of Atherosclerosis (MESA) participants. Self-reported intentional physical activity in the lowest quartile (0–105 MET-minutes/week) was categorized as inactive and the upper three quartiles (123–37,260 MET-minutes/week) as active. Associations of body mass index (BMI) and waist circumference categories, stratified by physical activity status (inactive or active) with cardiometabolic risk factors (dyslipidemia, hypertension, upper quartile of homeostasis model assessment of insulin resistance [HOMA-IR] for population, and impaired fasting glucose or diabetes) were assessed using logistic regression analysis adjusting for age, gender, race/ethnicity, and current smoking.Results:Among obese participants, those who were physically active had reduced odds of insulin resistance (47% lower; P < .001) and impaired fasting glucose/diabetes (23% lower; P = .04). These associations were weaker for central obesity. However, among participants with a normal waist circumference, those who were inactive were 63% more likely to have insulin resistance (OR [95% CI] 1.63 [1.24–2.15]) compared with the active reference group.Conclusions:Physical activity was inversely related to the cardiometabolic risk associated with obesity and central obesity.

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Clinical Measures of Physical Fitness Predict Insulin Resistance in People at Risk for Diabetes

Physical Therapy ◽

10.2522/ptj.20080064 ◽

2008 ◽

Vol 88 (11) ◽

pp. 1355-1364 ◽

Cited By ~ 31

Author(s):

Chiao-Nan Chen ◽

Lee-Ming Chuang ◽

Ying-Tai Wu

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Body Mass Index ◽

At Risk ◽

Risk Factor ◽

Waist Circumference ◽

Physical Fitness ◽

Clinical Measures

Background and Purpose Physical inactivity has been well documented as a risk factor for type 2 diabetes. Previous studies measured the level of physical activity either with questionnaires or with direct measurements of maximum oxygen uptake. However, questionnaires are patient-report measures, and methods for obtaining direct maximum oxygen uptake measurements often are not available clinically. The purpose of this study was to investigate whether clinical measurement of health-related physical fitness with a simple test battery can predict insulin resistance, a precursor of type 2 diabetes, in people at risk for diabetes. Subjects and Methods A total of 151 volunteers with at least one diabetes risk factor (overweight, hypertension, dyslipidemia, family history, impaired glucose tolerance, gestational diabetes, or delivering a baby weighing more than 4.0 kg) were recruited. Insulin resistance (as determined with the homeostasis model assessment of insulin resistance [HOMA-IR]), physical fitness (including body composition, as determined with the body mass index and waist circumference), muscle strength (handgrip strength [force-generating capacity]), muscle endurance (sit-up test), flexibility (sit-and-reach test), and cardiorespiratory endurance (step test) were measured, and a physical activity questionnaire was administered. Backward regression analysis was used to build the prediction models for insulin resistance from components of physical fitness and physical activity. Results Body mass index, muscle strength, and cardiorespiratory fitness predicted HOMA-IR in men (adjusted R2=.264). In women, age, waist circumference, and cardiorespiratory fitness were the predictors of HOMA-IR (adjusted R2=.438). Discussion and Conclusion Clinical measures of physical fitness can predict insulin resistance in people at risk for diabetes. The findings support the validity of clinical measures of physical fitness for predicting insulin resistance in people at risk for diabetes.

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No associations of prenatal maternal psychosocial stress with fasting glucose metabolism in offspring at 5–6 years of age

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174414000300 ◽

2014 ◽

Vol 5 (5) ◽

pp. 361-369 ◽

Cited By ~ 9

Author(s):

A. E. van Dijk ◽

M. van Eijsden ◽

K. Stronks ◽

R. J. B. J. Gemke ◽

T. G. M. Vrijkotte

Keyword(s):

Insulin Resistance ◽

Sex Differences ◽

Glucose Metabolism ◽

Psychosocial Stress ◽

Job Strain ◽

Fasting Glucose ◽

Stress Hormones ◽

Daily Hassles ◽

C Peptide ◽

Cumulative Score

Highly prevalent maternal psychosocial complaints are accompanied by increases in glucocorticoid stress hormones, which may predispose the offspring for type 2 diabetes and cardiovascular disease later in adulthood. The aim of the current research is to study whether prenatal maternal psychosocial stress is associated with parameters of blood glucose metabolism in their children aged 5–6 years. The study design was a prospective birth cohort (the Amsterdam Born Children and their Development study, the Netherlands). Depressive symptoms, pregnancy-related anxiety, parenting daily hassles and job strain were recorded by questionnaire (gestational week 16). A cumulative score was also calculated. Possible sex differences in the associations were considered. The subjects were 1952 mother–child pairs. Outcome measures were fasting glucose (n=1952), C-peptide and insulin resistance (HOMA2-IR) (n=1478) in the children at the age of 5–6 years. The stress scales, single and cumulative, were not associated with glucose/C-peptide/insulin resistance (allP>0.05). We did not find evidence for sex differences. In conclusion, we did not find evidence for an association between psychosocial stress during early pregnancy and parameters of glucose metabolism in offspring at the age of 5–6 years. Differences emerging later in life or in response to a metabolic challenge should not be ruled out.

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The effect of combination therapy of insulin glargine, metformin, and sitagliptin on insulin secretion, insulin resistance, and metabolic parameters in obese subjects with type 2 diabetes

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1610497z ◽

2016 ◽

Vol 144 (9-10) ◽

pp. 497-502

Author(s):

Teodora Beljic-Zivkovic ◽

Milica Marjanovic-Petkovic ◽

Miljanka Vuksanovic ◽

Ivan Soldatovic ◽

Dobrila Kanlic ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Body Mass Index ◽

Waist Circumference ◽

Insulin Glargine ◽

Body Mass ◽

Fasting Glucose ◽

C Peptide ◽

Obese Subjects

Introduction. A combination of drugs is required for treatment of obese subjects with diabetes, due to multiple pathogenic mechanisms implicated in the development of both diabetes and obesity. Objective. Assessment of the effect of sitagliptin added to insulin glargine and metformin, in obese subjects with type 2 diabetes. Methods. A total of 23 obese subjects on metformin and insulin glargine participated in the study. Titration of insulin glargine during a one-month period preceded the addition of 100 mg of sitagliptin daily. Body mass index, waist circumference, fasting, and prandial glucose were measured monthly, lipids and hemoglobin A1c (HbA1c) every three months, insulin, c-peptide and glucagon at the start and after six months of treatment. Homeostatic models for insulin secretion (HOMA B) and insulin resistance (HOMA IR) were calculated. Results. Participants were 58.65 ?} 7.62 years of age with a body mass index of 35.06 ?} 5.15 kg/m2, waist circumference of 115.04 ?} 15.5 cm, and the duration of diabetes of 4.11 ?} 2.57 years. With the titration of insulin glargine, target fasting glucose levels were not achieved. Waist circumference and body mass index decreased during three months of sitagliptin treatment, thereafter remaining stable. HbA1c decreased significantly after three and six months of therapy. C-peptide increased significantly, while glucagon level fell. HOMA indexes were unchanged. Conclusion. Sitagliptin can improve diabetes control and induce modest weight loss in obese subjects poorly controlled on insulin glargine and metformin. Titration of insulin glargine to optimal fasting glucose values is a prerequisite of success of this combination therapy.

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O-163 Hyperandrogenaemia in early adulthood is an independent risk factor for abnormal glucose metabolism in later life

Human Reproduction ◽

10.1093/humrep/deab127.031 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

K Tuorila ◽

M M Ollila ◽

M R Järvelin ◽

J Tapanainen ◽

S Franks ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Metabolism ◽

Fasting Glucose ◽

Early Adulthood ◽

Positive Association ◽

Population Based ◽

Androgen Excess ◽

Abnormal Glucose Metabolism ◽

Increased Risk

Abstract Study question What is the role of androgen excess as a contributing factor to insulin resistance and abnormal glucose metabolism (AGM) in women? Summary answer There was a positive association between early adulthood hyperandrogenaemia with AGM. Serum SHBG levels could help identifying women at risk for disordered glucose metabolism. What is known already It is commonly recognised that insulin resistance induces compensatory hyperinsulinaemia which promotes ovarian androgen secretion. Studies in rodents have also suggested that testosterone causes prolonged activation of androgen receptor in pancreatic islet β-cells, inducing insulin hypersecretion and eventually secondary β-cell failure, thus predisposing to type 2 diabetes (T2D). However, the exact physiology behind the association between androgens, insulin resistance and T2D in women is not well understood. Many previously published studies are limited by cross-sectional study design, unrepresentative clinic populations, as well as variying steroid hormone measurement methods and definitions of androgen excess. Study design, size, duration A prospective longitudinal population-based cohort (n = 5,889) to investigate whether serum levels of testosterone (T, measured using LC-MS/MS) and free androgen index (FAI) at ages 31 and 46 associated with AGM at age 46 years. After exclusion of pregnant women, users of hormonal intrauterine device, contraceptive pills, hormone therapy, minipills and statins, there were 4,421 women at age 31 and 4,457 women at age 46. At age 46 a two-hour OGTT was performed in 2,780 women. Participants/materials, setting, methods Serum fasting glucose and insulin, insulin resistance (HOMA–IR) and pancreatic β-cell function (HOMA–B) assessments were performed at ages 31 and 46. Elevated T levels (age 31: >2.3nmol/l; age 46: >1.7nmol/l) were defined according to the 97.5% percentile. T2D diagnoses were gathered from postal questionnaire at age 46, and verified and completed from the hospital discharge and national medication reimbursement registers. Impaired fasting glucose, impaired glucose tolerance or T2D were categorised as AGM. Main results and the role of chance At age 31, hyperandrogenic (HA) women displayed increased insulin resistance estimated by HOMA-IR (1.35±0.96 vs. 1.03±0.44, P = 0.05), increased insulin secretion estimated by HOMA-B (115.05±34.67 vs. 99.25±25.47, P = 0.006), and higher fasting insulin level (10.48±7.54 mU/l vs. 7.93±3.42 mU/l, P = 0.034) compared with normoandrogenic (NA) women, after BMI adjustment. At age 46, HA women had comparable HOMA-B levels (98.04±60.03 vs. 96.27±65.89, P = 0.93) but their fasting glucose (5.57±1.06 mmol/l vs. 5.37±0.77 mmol/, P = 0.07) and glycated haemoglobin levels (37.47±7.83 mmol/mol vs. 36.18±4.99 mmol/mol, P = 0.07) tended to be higher. Women in the highest T quartile (Q4 odds ratio [OR]=1.77, 95%CI: [1.14–2.76]) and in the two highest FAI quartiles at age 31 (Q4: OR = 3.61 [2.16–6.03] and Q3: OR = 2.11 [1.24–3.59]) had increased risk for AGM at age 46, independently of BMI, when compared with women in the lowest quartile. Similarly, women in the two highest FAI quartiles at age 46 had increased risk for AGM (Q4: OR = 2.91 [1.82–4.64]) when compared with women in the lowest quartile, after BMI adjustment. The three highest sex hormone-binding globulin (SHBG) quartiles inversely associated with AGM, both at ages 31 and 46, independently of BMI (at age 31: Q4: OR = 0.38 [0.24–0.62], at age 46: Q4: OR = 0.27 [0.17–0.44]). Limitations, reasons for caution We used only serum T as a marker of HA, even though other androgens, such as androstenedione and adrenal androgens have a place in the evaluation of androgenicity in women. Further studies of other large populations are needed to confirm our results. Wider implications of the findings This is the first longitudinal, general population based study to confirm a positive association between early adulthood hyperandrogenaemia with AGM in middle adulthood independently of confounding factors. Our results further suggest that SHBG levels could help to identify women at risk for AGM. Trial registration number NA

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Abstract 11965: Cardiovascular Risk Factor Reduction Through a Paleolithic Diet

Circulation ◽

10.1161/circ.132.suppl_3.11965 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Connor McKechnie ◽

Madeline McKechnie ◽

Julia McKechnie ◽

Ronald McKechnie ◽

Deepak Talreja

Keyword(s):

Insulin Resistance ◽

Blood Pressure ◽

Weight Loss ◽

Risk Factor ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factor ◽

Particle Number ◽

Fasting Glucose ◽

Paleolithic Diet ◽

Health Screen

Introduction: The paleolithic diet consists of grass-fed pasture-raised meats, seafood, vegetables, and also includes fruits, seeds, nuts and eggs. This diet has been shown to contribute to weight loss and mimics the diet our hunter-gatherer ancestors may have consumed. Weight loss is achieved through avoiding refined sugars, starches, dairy and legumes while consumption of protein, carbohydrates, and fat is relatively balanced. Objective: To study the effect of the paleolithic diet on the cardiovascular risk factor profiles of adults in the Hampton Roads area of Virginia. Methods: 35-85 year old non-diabetic adults, with one or more cardiovascular risk factor, were invited to participate. A comprehensive nutritional education program was provided to each participant prior to the 60-day intervention. Baseline weight, blood pressure, fasting glucose, hemoglobin A1c, high-sensitive C-reactive protein, fasting lipid panel and NMR Lipoprofile were assessed through an initial health screen. Each participant maintained daily food logs and met weekly with the multi-disciplinary study team to review their logs. The health screen was repeated after the 60-day intervention and intake logs were evaluated. Results: Weight loss averaged 12 lbs (6.7%, p=0.092). VLDL-particle number (VLDL-P, p=0.045), triglycerides (p=0.003), and HDL-particle number (p=0.011) levels significantly decreased. LDL-particle number (LDL-P) and LDL-cholesterol (LDL-C) did not significantly change, nor did fasting glucose or HbA1c. Blood pressure significantly improved (systolic, p<0.0001; diastolic, p=0.0003). Participants in the lowest tertile for weight loss had higher baseline risk factors including BMI, LDL-P, LDL-C, fasting glucose and HbA1c levels, yet lower baseline VLDL-P, triglycerides and blood pressure. Greater weight loss was associated with greater reductions in VLDL-P, triglycerides and lipoprotein insulin resistance index. Conclusions: The paleolithic diet promoted cardiovascular risk factor modification through weight loss, improved blood pressure, reduced triglyceride, and reduced lipoprotein markers associated with insulin resistance.

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Fasting insulin reflects heterogeneous physiological processes: role of insulin clearance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00013.2011 ◽

2011 ◽

Vol 301 (2) ◽

pp. E402-E408 ◽

Cited By ~ 36

Author(s):

Mark O. Goodarzi ◽

Jinrui Cui ◽

Yii-Der I. Chen ◽

Willa A. Hsueh ◽

Xiuqing Guo ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Secretion ◽

Waist Circumference ◽

Mexican Americans ◽

Fasting Glucose ◽

Insulin Clearance ◽

Oral Glucose ◽

Metabolic Clearance ◽

Insulinogenic Index ◽

Fasting Insulin

Several processes contribute to variation in fasting insulin concentration, including fasting glucose, insulin resistance, insulin secretion, and insulin clearance. Our goal was to determine the relative contribution of each of these insulin-related traits, plus anthropometric parameters, to fasting insulin among 470 Mexican Americans. The euglycemic hyperinsulinemic clamp yielded insulin sensitivity (M value) and metabolic clearance rate of insulin (MCRI). Acute insulin secretion was estimated by the insulinogenic index (IGI30) from the oral glucose tolerance test. Regression (univariate) and generalized estimating equations (multivariate) were used to describe the relationship of insulin-related traits to fasting insulin. Univarate analyses were used to select which traits to include in the multivariate model. In multivariate analysis, MCRI, M, BMI, waist circumference, and fasting glucose were independently associated with fasting insulin. Decreasing M and MCRI were associated with increasing fasting insulin, whereas increasing BMI, waist circumference, and fasting glucose were associated with increasing fasting insulin. Standardized coefficients allowed determination of the relative strength of each trait's association with fasting insulin in the entire cohort (strongest to weakest): MCRI (−0.35, P < 0.0001), M (−0.24, P < 0.0001), BMI (0.20, P = 0.0011), waist circumference (0.16, P = 0.021), and fasting glucose (0.11, P = 0.014). Fasting insulin is a complex phenotype influenced by several independent processes, each of which might have its own environmental and genetic determinants. One of the most associated traits was insulin clearance, which has implications for studies that have used fasting insulin as a surrogate for insulin resistance.

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Waist circumference and cardiorespiratory fitness are independently associated with glucose tolerance and insulin resistance in obese women

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2013-0160 ◽

2014 ◽

Vol 39 (3) ◽

pp. 358-362 ◽

Cited By ~ 4

Author(s):

Einat Shalev-Goldman ◽

K. Ashlee McGuire ◽

Robert Ross

Keyword(s):

Insulin Resistance ◽

Waist Circumference ◽

Glucose Tolerance ◽

Cardiorespiratory Fitness ◽

Fasting Glucose ◽

Tolerance Test ◽

Fasting Insulin ◽

Obese Women ◽

Insulin Metabolism ◽

The Relationship

The purpose of this study was to determine the independent associations between physical activity (PA), cardiorespiratory fitness (CRF), abdominal obesity and insulin action in obese women. We studied 141 abdominally obese women (waist circumference (WC): 106.4 ± 10.2 cm). PA duration (min/day) and intensity (counts/min) were obtained by accelerometry. CRF was measured using a treadmill. WC was measured at the iliac crest; abdominal adiposity was measured by magnetic resonance imaging. Glucose and insulin measures were obtained during a 75-g, 2-h glucose tolerance test. The homeostasis model of assessment iHOMA2-IS was used to estimate insulin sensitivity. PA duration and intensity were not associated with glucose or insulin metabolism (p > 0.05). However, moderate-to-vigorous PA (MVPA) duration was associated with fasting insulin and iHOMA2-IS (p < 0.01). CRF was associated with fasting insulin and iHOMA2-IS (r = 0.27, p ≤ 0.01), whereas WC was associated with fasting insulin (r = 0.50, p < 0.01) and iHOMA2-IS (r = –0.52, p ≤ 0.01). Following adjustment for CRF, MVPA, and age, WC remained associated with fasting glucose, insulin, 2-h glucose and iHOMA2-IS (r = –0.44, p ≤ 0.01). CRF was associated with fasting glucose as well as 1- and 2-h glucose (r = 0.24, p < 0.01) after adjusting for WC, MVPA, and age. MVPA was not associated with glucose or insulin measures after control for CRF and WC (p > 0.05). Mediation analysis revealed that CRF and WC combined mediated the relationship between MVPA and both glucose tolerance and insulin resistance (p < 0.05). In conclusion, among abdominally obese women, WC and CRF are independently associated with measures of glucose tolerance and insulin resistance and mediate the association between MVPA and insulin resistance.

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Size at birth is associated with blood pressure but not insulin resistance in 6–8 year old children in rural Nepal

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174410000103 ◽

2010 ◽

Vol 1 (2) ◽

pp. 114-122 ◽

Cited By ~ 3

Author(s):

C. P. Stewart ◽

P. Christian ◽

K. J. Schulze ◽

U. S. Shah ◽

G. Subedi ◽

...

Keyword(s):

Insulin Resistance ◽

Blood Pressure ◽

Birth Weight ◽

Waist Circumference ◽

Inverse Association ◽

High Waist Circumference ◽

Increased Risk ◽

High Prevalence ◽

Rural Nepal ◽

Size At Birth

Earlier, we reported that antenatal micronutrient supplementation reduced the risk of metabolic syndrome and microalbuminuria among offspring at 6–8 years of age in rural Nepal. In the same birth cohort, we examined associations of size at birth (weight, length and ponderal index), and gestational age, with cardiometabolic risk factors in childhood across all antenatal micronutrient interventions. There was an inverse association between birth weight and systolic blood pressure (SBP,β= −1.20 mm Hg/kg; 95% confidence interval (CI): −1.93, −0.46) and diastolic blood pressure (DBP,β= −1.24 mm Hg/kg; 95% CI: −2.00, −0.49). Current child body mass index was positively associated with SBP but not with DBP. Birth weight was unassociated with insulin resistance, but each kilogram of increase was associated with a reduced risk of high triglycerides (odds ratio (OR) = 0.64/kg; 95% CI: 0.41, 0.97) and an increased risk of high waist circumference (OR = 3.16/kg; 95% CI: 2.47, 4.41). In this rural Nepalese population of children 6–8 years of age with a high prevalence of undernutrition, size at birth was inversely associated with blood pressure and triglycerides and positively associated with waist circumference.

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